DESCRIPTION: Oral mucositis is a major dose-limiting toxic effect of intensive cancer chemotherapy and radiotherapy. In addition to the morbidity directly caused by severe oral mucositis, it can cause secondary morbidities by limiting oral intake or even lead to dose reduction or delay in further cancer treatment. Mucositis can be caused directly by cytotoxic effects and indirectly by sustained neutropenia after cytostatic therapy. An impaired mucosal barrier predisposes patients to life-threatening septic complications during aplasia. The prevalence of an oral focus in febrile neutropenia has been reported in up to 30 percent of cases. [unreadable] [unreadable] Recombinant human lactoferrin (rhLF) has been shown in pre-clinical experiments to exhibit a combination of immunomodulatory, anti-inflammatory and anti-infective properties. Lactoferrin has been shown to (i) promote healing in several in-vitro and animal models; (ii) inhibit increases in gut permeability induced by irritant agents in animal models and in humans; (iii) decrease the permeability of the gut mucosa to bacteria; (iv) reduce mortality following oral bacterial challenge in animal models; and (v) decrease the severity of neutropenic fever in patients receiving myelosuppressive chemotherapy for acute myelogenous leukemia. These properties make rhLF a promising candidate to prevent and treat severe oral mucositis and to reduce its systemic infectious complications. [unreadable] [unreadable] Based on the above results, we propose a Phase IIa clinical trial in patients at risk of developing severe oral mucositis. The target population is patients undergoing aggressive chemotherapy for the treatment of acute myelogenous leukemia, a therapy known to cause a high incidence of severe mucositis. The patients will receive either rhLF or placebo following completion of the chemotherapy and we will evaluate the ability of rhLF to reduce the incidence, severity, or duration of the oral mucositis, and its effect on the incidence and severity of neutropenic fever. [unreadable] [unreadable] In addition to the results described above which support the potential efficacy of rhLF in oral mucositis, the drug has been shown to be safe and well tolerated, having been administered orally to 210 patients without a single drug-related serious adverse event. The support we are requesting will enable us to continue clinical development of this novel drug and bring it closer to use by patients. [unreadable] [unreadable]